Fluid sample collection and delivery system and methods particularly adapted for body fluid sampling

ABSTRACT

There is disclosed apparatus for transporting a sample of body fluid such as blood from a first location to a remote test site location. The apparatus operates in conjunction with a fluid manifold module which has a first sample input port, a second washing fluid input port and a third input port for receiving air. There are tubing means coupled to said first, second and third input ports which are coupled together and coupled to a sample output line which extends from the first location to the remote location. The manifold means contains check valves with one valve for blood and one valve for washing fluid and a diaphragm pump for air. There are logic means which selectively operate the valves and pump to allow the sample line to receive a sample separated by air barriers from washing fluid solution. In this manner, a predetermined volume of sample is transported from the first location to the remote test site location. At the test site location, the presence of sample is detected by detection means and the sample is directed to a test site. The remainder of materials such as the washing fluid and air are discharged at the remote location. The system includes flexible tubing and the fluids as present are pumped from the first locaiton to the remote location by means of a peristaltic pump or other pump in direct contact with the tubing.

BACKGROUND OF THE INVENTION

This invention relates to a therapy control system for body fluidsampling and more particularly to blood sampling apparatus and methodswhich operate to collect a sample of blood, to transport that sample ofblood to a location remote from the site of sample collection andthereafter to dispense the blood sample such that in vitro diagnosticblood tests may be performed.

Modern medical procedures require numerous tests to be performed onblood samples in regard to clotting characteristics, blood gasconcentrations, blood chemistries and various other tests. These testsare required for a patient under treatment in a hospital or otherfacility. In typical techniques blood is usually manually drawn from thepatient's vein, artery or from tubing through which the patient's bloodis circulated external to the body. The amount of blood drawn and thefrequency of collection from a patient is a function of the number oftests that have to be performed. In any event, a relatively large numberof blood samples are frequently required at great inconvenience to themedical staff and discomfort to the patient.

The monitoring of a hospital patient's condition, particularly thoseconfined to intensive care or undergoing various surgical orvascular-invasive procedures, is often accomplished by means of testingblood samples collected at regular time intervals. These means usuallyrequire the use of a needle for collection of from 3 to 10 ml. of bloodper test. Traditional methods of collecting and testing such bloodsamples are wasteful, cumbersome and time consuming. Thus, it is usualfor such sampling to be limited by practical considerations to intervalsof 6 to 24 hours in the clinical situation and, with considerablygreater difficulty, to intervals as short as every 15 to 30 minutes insurgical and vascular-invasive procedures. The resultant data frequentlymisses rapidly changing physiological conditions that are of clinicalsignificance.

It is, therefore, an object of the present invention to provide a systemwhereby one can repeatedly collect and transport discrete blood samplesby means of various conduits or tubes to a test site or suitablecontainer. As will be explained, the apparatus operates to directsamples of blood taken directly from a patient or in vivo reservoir. Inthis manner the apparatus operates to direct the blood samples to a testsite or suitable container that can be remotely located from thephysical location of the patient and where various tests can beperformed on the samples.

It is a further object of the present invention to assure that theentire tubing and system components are automatically cleaned andflushed prior to introduction into the system of the body fluid to betested. In this manner the entire procedure automatically transports theblood to a test site and does so without the fear of contamination ofthe blood samples or contamination of the patient by the apparatus or bythe methods of controlling the apparatus.

It is yet a further object of the present invention to provide controlof the size of the blood sample so as to meet the requirements of thetest apparatus adapted to this invention and limit the waste of patientblood.

It is still a further object of the present invention to draw a sampleof blood from an in vivo patient source and thereafter to maintain in anopen or unclogged condition the route through which that sample isdrawn.

PRIOR ART

It is well known to transport body fluids to be diagnostically analyzedthrough tubular conduits. Many such systems separate discrete samples ofthe fluid by means of bubbles of an immiscible fluid which, for example,may be a gas as air and so on. J. Isreeli in U.S. Pat. Nos. 3,230,776and 3,251,229 teaches that distinct blood samples may be aspirated fromcontainers, separated by air bubbles and transported serially to ananalyzer system. It is further noted that the action of the bubblesserves to aid in cleansing of the tubular walls to thereby limit crosscontamination between successive fluid samples. In U.S. Pat. No.3,241,432, Skeggs further teaches that alternate fluid segments withinthe tube may comprise a washing solution, further to cleanse said wallsbetween the fluid samples to be analyzed. This same principle isacknowledged in many other patents, including: K. Negersmith et al3,266,322; and A. Ferrari 3,252,327, which patents, in addition,demonstrate a tubular take-off probe through which air bubbles areaspirated following alternating immersions of the probe tip into opencontainers of sample fluids and washing liquids. It is also well knownto inject air into the tubular fluid stream to create fluid segmentationby an immiscible bubble as demonstrated in Kassel U.S. Pat. No.3,654,959, Apr. 11, 1972; Hrdina, U.S. Pat. No. 3,524,366, Aug. 18,1970; and W. J. Smythe, U.S. Pat. No. 3,826,615, Jul. 30, 1974. U.S.Pat. No. 3,695,281 issued Oct. 3, 1972 to L. P. Leon demonstrates thatthe injected air bubble size may be controlled. A. Ferrari Jr. et al,2,935,028 shows that proportioning fluid pumping rates may be achievedby simultaneous peristaltic pumping action on parallel elastomeric tubesof differing internal diameters. J. Isreeli, 3,582,234, Jun. 1, 1971teaches close tolerance adjustment of the flow rate of fluids controlledby a peristaltic pump by stretching the tubing to vary the internaldiameter accordingly.

SUMMARY OF THE INVENTION

Apparatus for transporting a sample of body fluid such as blood from afirst location to a test site location, comprising sample tubing meanshaving at a first end a sample input port, a second washing fluid suchas saline input port and a third input port for receiving a fluid whichis relatively immiscible with said sample, such as air, and said washingfluid and having at a second end an output port, and having secondwashing fluid tubing means coupled to said second washing fluid inputport, a first pumping means coupled to said sample tubing meansoperative to direct the flow of fluids to said output port, secondpumping means coupled to said second washing fluid tubing meansoperative to direct the flow of washing fluid through said secondwashing fluid input port into said sample tubing means and co-operativewith said first pumping means to control the ratio of fluid volumespumped by said first pumping means and said second pumping means in afirst mode of operation to thereby cause washing fluid to flow withinsaid sample tubing means from said washing fluid input port towards bothsaid sample input port and said output port, first valving means coupledto said sample tubing means operative when selected in a second mode ofoperation to impede the flow of fluids to said output port thereby todivert all the flow of washing fluid from said washing fluid inlet portto said sample inlet port, second valving means coupled to said secondwashing fluid tubing means operative when selected in a third mode ofoperation to impede the flow of washing fluid through said secondwashing fluid input port into said sample tubing means, third meteredpumping means coupled to said third input port for injecting acontrolled volume of said immiscible fluid through said third input portwhen selected in said first and third modes of operation to therebyproduce in said sample tubing means a series of discrete immisciblefluid bubbles dispersed within said body fluid or said washing fluid,control means coupled to said pumping means and said valving means forselectively energizing said pumping and said valving means inpredetermined sequences to cause said output port to receive a givensequence of fluids as a series of cells of washing fluid separated bybubbles of said immiscible fluid in said first mode of operation or as aseries of cells of body fluid separated by bubbles of said immisciblefluid following said third mode of operation, said output port directedto a remote location including said test site, said sample tubing meanshaving detecting means at said remote location for monitoring saidsequence of fluids and for providing output signal levels indicative ofsamples, washing fluid and immiscible fluid at said remote location and,means coupled to said sample tubing means and responsive to said outputsignal levels for moving said second end of said sample tubing to saidtest site location when said output signal is indicative of the presenceof sample as contained in said series of cells of body fluids wherebyonly the contents of one selected cell of body fluid is directed to saidtest site location when said second end is moved and for discarding saidbody fluid, washing fluid and immiscible fluid in response to saidsignal levels when the selected cell of body fluid is not detected.

BRIEF DESCRIPTION OF THE FIGURES

FIG. 1, is a block diagram depicting a repetitive discrete sample bodyfluid sampling apparatus according to this invention.

FIGS. 2A-2K depict schematic diagrams showing the exact stepsimplemented by the apparatus in order to transport a sample of bloodfrom a patient site to a test site.

FIG. 3 depicts a practical system for blood sample collection, remotesite delivery and diagnostic analysis.

FIG. 4 is a perspective plan view of a fluid manifold and bubbledetector assembly comprising a series of interlocked planar members.

FIG. 5 is a side plan view of the fluid manifold of FIG. 4.

FIG. 6 is a schematic perspective plan view of a pump cassette assemblyemployed with the therapy control system according to this invention.

DETAILED DESCRIPTION OF THE FIGURES

Referring to FIG. 1, there is shown a block diagram of a repetitivediscrete blood sampling apparatus according to this invention. It is ofcourse understood that while the system depicted can deliver bloodsamples to a test site or suitable container any body fluid can beaccommodated as well and hence the system can be referred to as a fluidsample collection and delivery system. As seen in FIG. 1, there is showna blood sample supply line or flexible sample transfer tube 1,terminated at an inlet end with a catheter 4. The catheter 4 may beinserted directly into a patient's blood vessel or an extracorporealsource of fluid to be analyzed. An outlet end of transfer tube 1 iscoupled to a sample delivery nozzle 7 that is associated with a bloodsample analyzer 50. Blood sample analyzers 50 are widely available andsuch equipment operates to analyze or perform tests on dispensed bloodsamples. Shown coupled to the nozzle 7 and the tube is a module 52designated as TS/WS/SS. This module 52 may be a solenoid or other devicewhich pushes tube 1 and nozzle 7 from a test site (TS) location to awaste site (WS) location or a sample site (SS) location. As will beexplained, the system via the detector 31 determines when a true bloodsample is at the nozzle 7 and dispenses the sample at the test site tothe analyzer 50 or a suitable sample container at a sample deliverysite. In all other modes the nozzle 7 releases the fluids into a wastereceptacle at a waste site or a suitable sample container. When a trueblood sample is at nozzle 7 logic control 40 operates the TS/WS/SSmodule 52 to position the nozzle at the test site from the waste orsample site. As one can ascertain many devices can operate to do so. Theblood sample transfer tube 1 may consist of a plastic tube ofapproximately 0.085 inches outer diameter and having an inner diameterof 0.040 inches by way of example.

A washing fluid solution inlet port 12 is coupled to transfer tube 1 ata point as close to the catheter 4 as practical, as four to six inchesfor example. The term "washing fluid" includes isotonic solutions suchas an injectable normal saline. A second inlet port 13 is coupled totransfer tube 1 approximately one inch from washing fluid solution inletport 12 on the side opposite the inlet end. The inlet port 13 isemployed for introduction of a fluid which is relatively immiscible withthe blood sample and washing fluid solution. The impellers of aperistaltic pump 25 co-act with transfer tube 1 over a section 6 nearsample delivery nozzle 7 to create a peristaltic action for drawingfluid through transfer tubing 1 and out to nozzle 7. Peristaltic pumpswhich operate to direct or pump fluid within a flexible tube are wellknown and many examples of such pumps exist in the prior art. While asingle pump is shown to drive the washing fluid and sample lines it isunderstood that first and second pumps can be employed as well. Ifseparate pumps are employed the control of the flow rate is simplified.However one can configure the impellers or fingers of a simple pump 25to obtain isolation between the washing fluid and sample lines as drivenby a single pump. For purposes of minimizing sequential blood samplecross contamination, transfer tube 1 comprises as nearly as possible asingle uninterrupted length of extruded elastomeric tubing, as siliconeplastic for example, the surfaces of which are essentially hydrophobicand otherwise nonadherent to blood or liquid-blood-born medications ortransformed blood components. Inlet ports 12 and 13 and catheter 4attachment to transfer tube 1 are so constructed as to minimize theproduction of areas of fluid stagnation that might transfer residuesbetween blood samples, as will be explained.

A washing fluid solution delivery tube 2 is coupled to inlet port 12 byway of one-way valve 17 for transporting washing fluid from the washingfluid reservoir 9. The impellers or fingers of peristaltic pump 25co-act with the washing fluid delivery tube 2 over the samecorresponding section 6 as with the sample tube to cause injection ofwashing fluid through washing fluid inlet port 12 into transfer tube 1.One-way valve/1, prevents periodic partial reversal of flow in washingfluid delivery tube 2 caused by the normal action of peristaltic pump25. This assures that blood in sample transfer tube 1 can never be drawnthrough washing fluid inlet port 12. In order to assure that a greatervolume of fluid may be caused to flow in washing fluid delivery tube 2than in blood sample transfer tube 1 sections of tubes 1 and 2 asdirected along area 6 are comprised of relatively identical elastomerictubings. A constant ratiometric flow between these two tubes is achievedby the slight stretching of transfer tubing 1, relative to washing fluidsolution delivery tube 2, as for example 10 percent. This stretch occursin area 6 where one tube is stretched with respect to the other tocontrol the flow volume. The sections 6 of tubes 1 and 2 are located ina cassette (FIG. 3) assembly which is associated with the pump and aninstrument housing as will be explained. Thus, washing fluid may attimes be injected into transfer tube 1 by way of inlet port 12 at a rateproportionally greater than the rate at which the peristaltic pump 25draws fluid through transfer tube 1. A diaphragm-type pressure switch 33connected to washing fluid delivery tube 2 serves to detectover-pressure conditions in both sample transfer tube 1 and washingfluid delivery tube 2 indicative of occlusion of catheter 4 or of thevessel from which blood samples are being collected.

The outlet of a fixed volume diaphragm pump 14 is directly connected toinlet port 13 of transfer tube 1 for injecting controlled volume bubblesof an immiscible fluid, such as air, into transfer tubing 1. The inletto diaphragm pump 14, not shown, may be opened directly to ambient airor ducted by tubing means to a reservoir of the immiscible fluidmaterial such as a non-volatile fluorocarbon liquid. A solenoid drivenpneumatic pump 24 driven by a control signal from logic controller 40sends a pressure pulse through the tube 3. This pulse drives thediaphragm pump 14 resulting in the injection of a controlled volumebubble of immiscible fluid into sample transfer tube 1 by way of inletport 13.

Shown associated with the transfer tube 1 is a first tubing pinch valve21 located at the inlet to the peristaltic pump. The valve 21 whenactivated, prevents the flow of fluids within transfer tube 1 betweeninlet port 13 and delivery nozzle 7. A second tubing pinch valve 22 isalso located at the inlet to peristaltic pump and associated withwashing fluid delivery tube 2. Valve 22, when actuated, prevents flow ofwashing fluid into transfer tube 1 by way of washing fluid inlet port12. Pinch valves 21 and 22 are controlled by the logic controller 40 topermit independent fluid flow at various times in sample transfer tube 1and washing fluid tube 2. As will be explained, valves 21 and 22 arelocated in the area adjacent to the cassette associated with the pump(FIG. 3). Peristaltic pumps in general provide a pulsed fluid flow. Thisoperation is employed to great advantage in the scrubbing node as due tothe pulse flow turbulences as achieved which enhances the scrubbingaction. In the keep open flow mode, relatively constant flow is achievedby compensating for the known pinch off period of the pump and causingan increase in pump speed to maintain a more constant flow. Thisoperation is achieved by monitoring the position of the rotationalposition of the pump so that the fluid pinch off zone is defined andusing this information to optimize fluid delivery.

A fluid detector 18 is associated with blood sample transfer tube 1 andlocated at a point between the catheter 4 and washing fluid inlet port12. The detector 18 identifies what fluid is passing within sampletransfer tube 1 and otherwise serves as a bubble detector. A secondfluid detector 31 associated with sample transfer tube 1 is located asclose as practical to outlet nozzle 7, one to two inches for example, toidentify what fluid is about to be dispensed.

Leads of the logic controller 40 are coupled through an output terminalboard 41 to drive motor 23 of the dual channel peristaltic pump 25,pneumatic pump 24, tubing pinch valves 21 and 22. By way of signal inputterminal board 41 controller 40 is connected to and is responsive tofluid or bubble detectors 18 and 31, and pressure switch 33 forcoordinating the flow of the blood sample, washing fluid, and immisciblefluid within sample transfer tube 1 thereby to transport the bloodsample from the inlet or catheter end to outlet or nozzle end.

Logic controller 40 is also adaptable to interface with various datainput and output devices as shown in FIG. 3. These may include a displaydevice 43, a keyboard 48, a printer (not shown), a standard datainterface such as RS232 and connections to blood testing devices andinfusion apparatus.

Logic controller 40 can be connected to all essential system functionsso as to provide the desirable monitoring of said functions ensuring ahigh level of performance and safety. Further, logic controller 40 hasthe capability to store monitored data in memory and recall, inpredetermined formats, pertinent data such as volume of blood drawnvolume of fluids infused, and number of samples taken.

All system functions are monitorable and controllable through logiccontrol 40 and the system is designed to provide maximum safety,comfort, performance, accuracy, and ease of use to the patient andclinician.

Control 40 can make certain decisions consistent with therapeuticpractice in response to signals received from fluid sampler, test deviceand infusion apparatus.

It will be understood that from a practical perspective it is convenientto organize the various system components described into functionalassemblies that place a minimum of hardware and attending patientdiscomfort at the site of sample fluid collection. Thus, inlet ports 12and 13, diaphragm pump 14 one-way valve 17 and fluid detector 18 are allincluded within an assembly module 11. Module 11 of small dimensions asone inch wide, two inches long and 0.5 inches thick for example. Such anassembly may be conveniently taped to a patient's arm in close proximityto the insertion site of catheter 4. Module 11 is connected by way of aflexible umbilical 8 of three to eight foot length for examplecomprising sample transfer tube 1, washing fluid delivery tube 2,pneumatic tube 3 and fluid detector control and output lines 19 toinstrument 51 (dashed lines) comprising the logic control 40, analyzer50, pumps, valves, actuators and detectors. A tubing connector 16 andmanual tubing pinch clamp 15 in washing fluid delivery tube 2 areprovided for convenience in changing washing fluid reservoir 9 duringinstrument operation. The module 11 is shown in detail in FIGS. 4 and 5and is referred to as a fluid manifold and bubble detector assembly.

For clarity in understanding the process of blood sample collection andsystem purging FIGS. 2A through 2K depict schematic detail of thecontents and states of sample transfer tube 1 at various phases ofoperation. Identical structural features in these schematic drawingsemploy the same numerical designations as utilized in FIG. 1.

In FIG. 2A there is shown the sample transfer tube 1 filled with washingfluid solution except in the immediate region of catheter 4. In thisphase of operation peristaltic pump 25 acting on the sample tubing 1along section 6 has commenced drawing blood 60 from vessel 10, throughcatheter 4 and into the inlet end of sample transfer tube 1. No fluidsare transferred in or out of sample transfer tube 1 at inlet ports 12and 13. Droplet 67 of washing fluid displaced by the pumping action isdispensed from nozzle 7.

In FIG. 2B there is shown sample transfer tube 1 at a slightly latertime as 0.25 seconds for example. Blood 60 has been drawn past inletports 12 and 13. It will be noted that some diffusion may cause blood toenter washing fluid inlet port 12, however the static condition ofwashing fluid in washing fluid delivery tube 2 otherwise inhibitssignificant penetration of blood into inlet port 12.

In FIG. 2C the condition in FIG. 2B is altered by the injection throughinlet 13 of a small volume of immiscible fluid as seven to tenmicroliters of air. This forms a bubble 65 in the tube 1 of saidimmiscible fluid. The bubble 65 fills an entire cross section of sampletransfer tube 1 but is of lineal extent not to exceed the lineardistance between inlet port 13 and washing fluid inlet port 12. Thebubble 65 creates an isolating barrier within the blood 60 that has beendrawn into sample transfer tube 1. By restricting the lineal extent ofbubble 65, it will be seen that reverse flow in sample transfer tube 1as later described cannot cause infusion of any portion of bubble 65into vessel 10.

FIGS. 2D and 2E depict the same system at relatively later times when asecond bubble 69 and third bubble 70 are caused to enter sample transfertube 1 thereby creating isolated blood columns 62 and 63 each of 10 to100 microliters for example. In function it is the purpose of leadingblood column 62 to collect any residue of washing fluid that may remainin contact with the inner surfaces of sample transfer tube after passageof bubble 69. The bubble 69 further assures that any additionalresiduals on the inner surface of sample transfer tube 1 after passageof blood column 62 are indicative only of the characteristics of blood60 alone as contained in isolated blood column 63. It will be understoodthat the number and lineal extent of isolated blood columns as 62 may beselected to best achieve the conditioning of the inner surfaces ofsample transfer tube 1 prior to passage of the isolated blood column 63that is to be analyzed.

FIG. 2F depicts the same system approximately 0.1 seconds later. Washingfluid solution 71 has begun to enter sample transfer tube 1 by way ofinlet port 12 at a rate slightly greater than the rate at which fluid isdrawn by peristaltic pump 25 through sample transfer tube 1. Thus, blood60 is caused to reverse its flow in sample transfer tube 1 at the entrypoint of washing fluid inlet port 12 and is reinfused into vessel 10 byway of catheter 4. It is the intent of such reverse flow to clear andmaintain the sample transfer tube 1 clear of all traces of blood 60between washing fluid inlet port 12 and catheter 4 and catheter 4 itselfas nearly as possible.

In FIG. 2G blood columns 62 and 63 have been directed further alongsample transfer tube 1 to the point where the second bubble 69 has beendetected by bubble detector 31 thereby identifying the location of theleading boundary of blood sample column 63. A train of bubbles 66 ofimmiscible fluid has been injected into the washing fluid contained insample transfer tube 1 between immiscible fluid inlet port 13 and bloodcolumn 63. The train of bubbles 66 is employed to provide a scrubbingaction on the inner surfaces of sample transfer tube 1 from inlet port13 to thereby remove blood 60 residue that may affect subsequent bloodsamples. The reverse flow of washing fluid between catheter 4 andwashing fluid inlet port 12 has caused all of the blood 60 previouslycontained in this tubing section to be reinfused into vessel 10.Thereafter, the continued reverse flow causes washing fluid to beinfused through catheter 4 into vessel 10, both cleansing the innersurfaces of the tubing and catheter 4 and maintaining a "keep openflow."

In FIG. 2H fluid has been further moved in sample transfer tube 1 to thepoint where the leading boundary of blood sample column 63 has beenadvanced to the open end of nozzle 7 and is ready for dispensing toblood testing device 50. Previously, fluid droplets as 67 in FIGS. 2Athrough 2H have been dispensed to a waste reservoir, not shown. Whenblood sample 63 is detected, the flexible tube end and nozzle 7 aremoved by means of a solenoid or other device by the logic control 40 todirect nozzle 70 at the test site. Thus the positioning of the bloodsample column is implemented by the logic control module 40 (FIG. 1).This is implemented by considering the given pre-set distance betweendetector 31 and the open end of nozzle 7 and known peristaltic pump 25characteristics.

In FIG. 2I a measured portion 59 of blood sample column 63 is dispensedto the blood testing device 50 located at the test site as determined bycontrol of peristaltic pump 25 by logic control module 40 in FIG. 1. Theentire process as depicted in FIGS. 2A through 2I may be accomplished in15 seconds for a sample transfer tube 1 length of 6 feet for example.

In FIG. 2J all of the blood previously remaining in sample transfer tube1 as in FIG. 2I has been expelled to the waste site. The entire volumeof sample transfer tube is now filled with washing fluid or combinationsof washing fluid and bubbles 66 as in FIG. 2G. It will be understoodthat the number and distance between bubbles in bubble train 66 (FIG.2G) and the time during which flow of washing fluid and immiscible fluidbubbles in sample transfer tube 1 is sustained may be variable to bestaccomplish the elimination of blood residues within the sample transfertube 1.

In FIG. 2K pinch valve 21, as operated by logic control, has blocked thesample transfer tube 1 inlet to peristaltic pump 25 such that continuedinflow of washing fluid through washing fluid inlet port 12 causes allof the washing fluid flow to be directed through catheter 4 into vessel10. At this point, the impelling action of peristaltic pump 25 on thewashing fluid delivery tube 2 may be reduced to maintain a normal keepopen washing fluid flow rate in catheter 4 as 5 milliliters per hour forexample. This is easily implemented by logic control 40.

It will be understood that the process steps depicted in FIGS. 2Athrough 2K are intended to achieve the functions of drawing a bloodsample to be tested, dispensing the sample to a test device at alocation remote from the site of sample collection, taking steps tomaintain the purity of the blood sample so that it remains essentiallyunaffected from an analysis perspective by its removal from the sourcevessel 10 and transfer the sample to blood testing device 50, cleaningthe surfaces contacted by the blood sample subsequent to the transferprocess, and establishing a keep open flow in the catheter 4,maintaining it clear of material such as clotted blood within the vessel10 after the sampling process has been completed. It will be furtherunderstood that the fixed volume of diaphragm pump 14 in FIG. 1 servesto prevent potentially dangerous injection of air or other immisciblefluid into the blood source vessel 10. Furthermore, it will beunderstood that air bubbles may in fact pass from washing fluid fluidreservoir 9 through washing fluid delivery tube 2. Thus, the bubbledetector 18 in FIG. 1 provides protection from immiscible fluid bubbleinjection into vessel 10 by signaling the logic control module of thepresence of such bubbles prior to such injection.

Referring to FIG. 3, there is shown a practical system for blood samplecollection, delivery to a remote site and diagnostic analysis. Simplydescribed, the system is divided into permanent and disposablecomponents. The permanent instrument section comprises visual monitorand data input module 43, blood sample collection and delivery systemmodule 51, and blood testing system module 50. These modules are housedin instrument housing 49 that is designed to be suspended from aconventional IV pole via clamps (not shown) or to sit on a convenienthorizontal surface. The disposable components include the fluid manifoldand bubble detector assembly module 11, tubing and electrical umbilicalbundle 8, cassette 34, and washing fluid washing fluid reservoir 9. Notshown are the blood testing device cassettes that reside behindinstrument access door 52, and the waste fluid container that residesbehind access door 53.

For operator convenience the blood sample disposable is provided as asingle assembly that includes catheter 4 connected directly to sampletransfer tube 1 and fluid manifold and bubble sensor assembly 11connected by way of tubing and electrical umbilical bundle 8 to cassette34. In use, cassette 34 is positioned in a recess 30 of the instrumenthousing 49. The umbilical 8 is then routed to the site of sampling.After insertion of the catheter 4 into the vessel containing blood to besampled, the fluid manifold and bubble sensor assembly 11 is taped orotherwise attached to structure adjacent to the site of catheter 4insertion. This site may be the patient's arm, for example, to therebyprovide strain relief for the sample transfer tube 1 and catheter 4 aswell as the umbilical 8. The fluid reservoir 9, is a conventional IVbottle or bag of normal washing fluid. The reservoir 9 is attached tothe cassette 34 by conventional tubing connector 16 and located adjacentto the instrument housing 49 as IV pole-mounted on the same pole towhich the instrument housing 49 is attached.

When properly positioned within the recess 30 of the instrument housing49, the sampler cassette 34 is maintained in direct contact withinterface surface 35, thereby establishing positional relationshipsbetween sample transfer tube 1 and washing fluid delivery tube 2. Thetubes 1 and 2 are routed through the cassette 34 and interface with thefingers of peristaltic pump 25, pinch valves 21 and 22, and bubbledetector 31. Electrical contacts with bubble sensor 18 power and signalwires 19 (FIG. 1) are also made between interface surface 35 andcassette 34. Pneumatic connection between air pump control tube 3 andpneumatic pressure pulse pump 24 (FIG. 1) is similarly establishedthrough interface surface 35.

As indicated above, the essence of the apparatus and method is that theequipment directs a sample of blood from a patient's vessel as an arteryor a vein or from an extra-corporeal tube through which fluid is beingpassed continuously. The apparatus can be employed in heart surgery withtubing that goes to the oxygenator or in dialysis wherein the fluid ispassed out of the body and goes into a processing unit that cleanses theblood. The unique features of the above-noted system as differentiatedfrom prior art systems is the fact that the collection site is a closedsite rather than an open cuvette. In order to keep the inlet clean, thesystem performs a reverse flow back into the patient utilizing a washingsolution which is compatible and non-toxic as for example a washingfluid or any non-toxic isotonic fluid.

Referring to FIG. 4, there is shown a fluid manifold and bubble detectorassembly 11 as for example depicted in schematic form in FIG. The module11 has entering therein the sample tube 1, the pneumatic air pumpcontrol tube 3, the washing solution or washing fluid delivery tube 2 aswell as the bubble detector power and signal wires 19. These tubes andwires are coupled together to form the umbilical 8 (FIG. 1). As one canascertain from FIG. 4, the fluid manifold and bubble detector assembly11 is fabricated from five planar interlocking layers of plasticmaterial designated as L1, L2, L3, L4 and L5. These planar plasticmembers are preconstructed and preformed and as will be explainedsandwich the series of tubes as indicated in FIG. 1 between the variouslevels. The planar members L1 to L5 also contain a check valve 17 andthe diaphragm air pump 14. L1 and L2 as shown sandwich two pieces oftubing therebetween. One tube is the sample line 1 and the other isdesignated as the bubble air in line. This line is just an air intakewhich supplies the air that goes into the sample line and under controlof the diaphragm pump 14. The tubes are positioned between L1 and L2 bymeans of congruent grooves or channels as 91, 92, 93 and 94.

The module L2 contains two check valves as well as two small ports whichinterface with the valves as will be explained. Essentially, the checkvalves 70 and 71 are disk like valves and operate to perform thefunction of assuring one way flow of washing fluid into the sample lineand diaphragm pump output of immiscible fluid into the sample line.Check valves 70 and 71 are made from silicon rubber, are molded and havea built-in compression seal so that upon assembly the check valve alsoperforms a through-face seal for fluid and air.

These check valves 70 and 71 enable uni-directional flow of air andwashing fluid into the sample line 1 and do not permit any backflow offluid into the air pump or backflow of fluid into the washing fluidsource line. The washing fluid check valve 71 is shown in FIG. 1 asvalve 17. The module 11 contains a diaphragm air pump 72 which islocated in planar member L3. The diaphragm air pump is close coupled onits output side to the sample line. The diaphragm air pump basically hasa flapper valve in 73 and a flapper valve out 71. The volume throughwhich the diaphragm travels limits the size of the bubble injected intothe sample line 1 regardless of how much pneumatic driving air pressureis applied to the diaphragm.

The diaphragm is a small disk forming a very tiny pump. The air bubblewhich is injected into the sample line for example is less than 50millionths of a liter. The small diaphragm with an appropriate seal fitsinto a well or depression in planar member L3.

As indicated above, the valves 70, 71 and 73 and the diaphragm pump 72each include an annular elastomeric disk or membrane with acircumferential flange. The flange acts as a seal. The drive air comesin through a port 74 (L4) that sits over the diaphragm of the pump. Theport 74 is directed into the drive air in tube 3, which is sandwichedbetween L4 and L5. The actual pumping action is performed by initiallydrawing a small vacuum which draws the diaphragm up and then it isdriven back down with very little air pressure. Essentially, thediaphragm operates to provide a fixed volume air bubble as long as thediaphragm operates through its full stroke. Thus there is a consistentair bubble size regardless of the amount of air pressure that drives thediaphragm. As one can ascertain, the washing fluid line 2 is directedthrough and sandwiched between planar members L4 and L5 and is portedstraight down to the layers L3 and L2 through the check valve 70 andappropriate apertures. As indicated, the purpose of the check valve 70is to prevent back flow into the washing fluid line. The washing fluidline 2 is ported to the sample line via apertures located in planarmodules L4, L3 and L2 as for example aperture 75 as shown in L4,corresponding aperture 76 in L3 and via the valve 70 through an aperturein L2 at which point the sample line is punctured by means of a pin orother device to provide a washing fluid port. The port allows couplingof the washing fluid line to the sample line through an aperture in thewashing fluid line and an aperture in the sample line which aperturescommunicate with the corresponding apertures in the planar modules(L1-L5).

As seen in FIG. 1, the diaphragm air pump 14 which is the diaphragm pump72 of FIG. 4 is driven directly by the pneumatic pressure pump 24 whichis controlled by the logic control 40 of FIG. 1. In any event, the portfor the pneumatic air pump control tube is also sandwiched betweenmodules L5 and L4 and is indicated as the Drive Air In line 3 whichfunctions as line 3 of FIG. 1. The air which is directed through thetube 3 also couples to the diaphragm 76 via apertures in module L4. One,of course, understands that the diaphragm pump 72 is completelyanalogous to the diaphragm air pump 14 of FIG. 1.

Thus as indicated, the diaphragm pump controls the size of the airbubble which is directed into the sample line. A typical bubble size isabout 1/4 of an inch or about 7 microliters but can be as much as 50microliters as controlled by the volume of the diaphragm pump 14. Thediaphragm in its relaxed state also serves as a check valve by coveringthe port to the air out valve 71 thus inhibiting the suctioning of airinto the sample line during sampling.

Again, referring to FIG. 4, it is understood that there are three fluidlines that are sandwiched between the planar modules L4 and L5. There isthe washing fluid IN line 2, the drive air IN line 3 and a linedesignated as IV through. This line is just a pass through port inmodule 11 that allows the user to run a tube back to a pump assembly.This is done if a hospital for example desires to run an intravenous(IV) line without having a separate line. In any event, an IV throughline could be accommodated within the fluid manifold and bubble detectorassembly 11 and could, in fact, be operated by the peristaltic pump orby a separate pump. As one can ascertain from FIG. 4, within planarmember L4 is a module designated by reference numeral 80 and this is thebubble detector as 18 of FIG. 1. The bubble detector wires emanatingfrom module L4 are designated by reference numeral 85. Essentially,bubble detectors are well known and typically they may include an LEDand photocell or other devices as well.

A bubble detector as 80 may operate on the principal that air is clearand hence when an air bubble passes by the detector 80, a maximum amountof light would be transmitted. Blood is darker than air and a minimumamount of light would be transmitted when blood is present. Such bubbledetectors as indicated are very well known in the art and there are verymany different types of devices which can be employed. Bubble detector80 is associated with a differentiator circuit whereby electronicallyone monitors the rate which a change occurs between one bubble type andanother. The rate of change gives a pulse at the start of a bubble todetect air, blood or washing fluid.

Referring to FIG. 5, there is shown a side view of the various planarmodules L1 to L5 shown in FIG. 4. The posts which are shown in FIG. 5 asfor example 87, 88, and 89 are actual pins to enable each of the planarmodules L1 to L5 to be coupled one to another via the pins 87, 88 andvia corresponding apertures. Hence each of the modules L1 to L5 areaccurately aligned by means of pins and apertures to interlock toprovide the module assembly 11. The various tubes are accommodated orsandwiched between the planar member via channels in the members whichaccommodate the tubes.

The various layers L1-L5 are connected together by means of ports orapertures in each of the layers to enable one to couple the sample line1 to the washing fluid line as well as to the source of air, asindicated.

Referring to FIG. 6, there is shown the blood sample collection systemdisposable cassette 34 as shown in FIG. 3. The sample transfer tube 1 isdirected through the cassette as is the pneumatic air pump control tube3 and the washing solution or washing fluid delivery tube 2. Thecassette has a front plate 29 which essentially includes a series ofindentations. The indentations form a washing fluid delivery tube guideor groove 27 and a sample transfer tube guide or groove 28. These guides27 and 28 accommodate the washing fluid line 2 and the sample line 1.The grooves 27 and 28 have flat bottom surfaces in order to allow thefingers of the peristaltic pump to coact with the tubes to control fluidflow. As can be seen, the cassette consists of a planar member 29 whichis the cassette back cover and a front planar member 47 which is thecassette front cover. Member 47 has a plurality of channels toaccommodate the various tubes as shown. It is also shown that the tubesfor example are conveniently coupled together by means of suitabledevices. The pump cassette assembly 34 also contains an occlusiondetector pressure sensor interface port 45. There is shown a sampledelivery nozzle pivot arm 36 to enable the cassette to be emplaced andremoved from in the housing 40 as shown for example in FIG. 3.

Sample delivery nozzle pivot arm 36 locates a section of the sample tube1 with respect to a bubble detector 31 shown in FIG. 1 which is locatedwithin the blood sample collection and delivery system module 51 shownin FIG. 3. This bubble detector 31 is used to detect and sense theposition of the fluids in the output end of sample tube 1.

The front cover of the cassette assembly 47 has an aperture 39 throughwhich the fingers of the peristaltic pump are directed and which engagethe sample line and the washing fluid line at areas 5 and 6 to pumpfluid in the lines as explained in regard to FIGS. 2A to 2K. Thus, asone can understand from the above, the system utilizes two disposablemodules. One module referred to as the fluid manifold detector assembly11 is completely disposable and can be placed as indicated on the arm ofthe patient. The module 11 is small and has the umbilical cord 8directed therefrom. The cord 8 is also disposable. After the patient hasbeen monitored accordingly, the entire module 11 and cord 8 is thrownaway. The second disposable module as shown in FIG. 6 is the therapycontrol or pump cassette assembly 34. This also contains tubings and thevarious other parts which can be disposed of. It is, of course,understood that the module 34 need not be disposable but can befabricated in two parts as a cassette assembly and rearranged for eachpatient for example by placing new tubing within the cassette assembly.

The sample line is stretched at area 6 with respect to the washing fluidline to change the ratio of the flow rates under the influence ofidentical peristaltic impeller action. The stretch typically changes theflow between 0 and 25 percent.

Thus, as indicated, there is described a system which is a bloodsampling apparatus system which allows one to take a sample of bloodfrom a vessel of a patient or extracorporeal port and which sample ispassed continuously to a test location. The entire system relies on thefact that the inlet or the collection site is a closed site. The inletsite can be cleaned by a back flushing operation whereby fluid flow isreversed and the entire monitoring procedure can operate continuouslyutilizing the same blood vessel. The system eliminates the need forconstant blood samples to be taken from a patient through finger pricksor other standard devices, while allowing continuous monitoring andtesting as desired.

We claim:
 1. Apparatus for transporting a sample of body fluid such asblood from a first location to a test site location, comprising:sampletubing means having at a first end a first sample input port, a secondwashing fluid input port and a third input port for receiving a fluidwhich is relatively immiscible with said sample and said washing fluidand having at a second end an output port, washing fluid tubing meanscoupled to said second washing fluid input port, a first pumping meanscoupled to said sample tubing means operative to direct the flow offluids to said output port, second pumping means coupled to said washingfluid tubing means operative to direct the flow of washing fluid throughsaid second washing fluid input port into said sample tubing means andco-operative with said first pumping means to control the ratio of fluidvolumes pumped by said first pumping means and said second pumping meansin a first mode of operation to thereby cause washing fluid to flowwithin said sample tubing means from said washing fluid input porttowards both said sample input port and said output port, first valvingmeans coupled to said sample tubing means operative when selected in asecond mode of operation to impede the flow of fluids to said outputport thereby to divert all the flow of washing fluid from said washingfluid input port to said sample input port, second valving means coupledto said second washing fluid tubing means operative when selected in athird mode of operation to impede the flow of washing fluid through saidsecond washing fluid input port into said sample tubing means, thirdmetered pumping means coupled to said third input port for injecting acontrolled volume of said immiscible fluid through said third input portwhen selected in said first and third modes of operation to therebyproduce in said sample tubing means a series of discrete immisciblefluid bubbles dispersed within said body fluid or said washing fluid,control means coupled to said pumping means and said valving means forselectively energizing said pumping and said valving means inpredetermined sequences to cause said output port to receive a givensequence of fluids as a series of cells of washing fluid separated bybubbles of said immiscible fluid in said first mode of operation or as aseries of cells of body fluid separated by bubbles of said immisciblefluid following said third mode of operation, said output port directedto a remote location including said test site, detecting means coupledto said sample tubing means at said remote location for monitoring saidsequence of fluids and for providing output signal levels indicative ofsamples, washing fluid and immiscible fluid at said remote location and,means coupled to said sample tubing means and responsive to said outputsignal levels for moving said second end of said sample tubing to saidtest site location when said output signal is indicative of the presenceof sample as contained in said series of cells of body fluids wherebyonly the contents of one selected cell of body fluid is directed to saidtest site location when said second end is moved and for discarding saidbody fluid, washing fluid and immiscible fluid in response to saidsignal levels when the selected cell of body fluid is not detected. 2.The apparatus according to claim 1 wherein said immiscible fluid is airand sample of body fluid is blood.
 3. The apparatus according to claim 1wherein said first and second pumping means includes a peristaltic pumpmeans having a series of fingers operative to pump fluid within a tubetowards a remote location with a first channel adapted to receive saidsample tubing means and a second channel adapted to receive said washingfluid tubing means with said channels positioned with respect to saidfingers to cause said pump to pump both sample and washing fluid viasaid tubing means.
 4. The apparatus according to claim 2, wherein saidwashing solution is injectable normal saline.
 5. The apparatus accordingto claim 3 wherein the diameter of said sample tubing means is differentfrom the diameter of said washing fluid tubing means to thereby obtain adifferent flow rate of sample with respect to washing fluid.
 6. Theapparatus according to claim 1 wherein said first sample input port iscoupled to a catheter for insertion into a blood accommodating vesselassociated with a patient.
 7. The apparatus according to claim 1 whereinsaid sample tubing means and said washing fluid tubing means includeflexible plastic tubes for accommodating said fluids.
 8. The apparatusaccording to claim 1 wherein said washing fluid input port is coupled toa washing fluid reservoir via a flexible plastic tube.
 9. The apparatusaccording to claim 5 wherein said first valving means is a pinch valveoperative when selected to pinch said sample tubing means to block theflow of fluid to said output port.
 10. The apparatus according to claim1 wherein said second valving means is a pinch valve operative whenselected to block the flow of washing fluid from said reservoir.
 11. Theapparatus according to claim 2 wherein said third metered pumping meansis a diaphragm pump coupled to a pressure pump for operating saiddiaphragm to provide a controlled volume of immiscible fluid to bedirected through said third input port to said sample tubing means. 12.The apparatus according to claim 1 wherein said detecting means is abubble detector operative to detect the transitions between said cellsof sample, washing fluid and immiscible fluid.
 13. The apparatusaccording to claim 1 including a fluid dispensing nozzle coupled to saidoutput port of said sample tubing means.
 14. The apparatus according toclaim 3 further including a bubble detector coupled to said sampletubing means near said catheter to detect any bubbles.
 15. Apparatus fortransporting a sample of body fluid such as blood from a first locationto a test site location, comprising:a fluid manifold means having afirst sample input port, a second washing fluid input port and a thirdinput port for receiving a medium which is relatively immiscible withsaid sample and said washing fluid, and having sample tubing meanscoupling said first, second and third input ports, said fluid manifoldmeans having selectively operable first pump means located thereon, withsaid first pump means coupled to said third input port to direct a cellof said immiscible fluid into said sample tubing means when said firstpump is operated with said cell operative to separate sample fromwashing fluid, control means coupled to said first pump means forselectively energizing said pump means in predetermined sequences tocause said sample tubing means to receive a given sequence of matter asa first volume of washing fluid followed by a second volume of saidimmiscible medium followed by a third volume of body fluid, followed bya fourth volume of immiscible medium followed by a fifth volume of bodyfluid, followed by a sixth volume of immiscible medium, followed by aseventh volume of washing fluid, said sample tubing means directed fromsaid manifold means at one end to a remote location including said testsite at an output end, said sample tubing means having detecting meansat said remote location for monitoring said sequence of matter and forproviding at an output signal levels indicative of sample, washing fluidand immiscible material at said remote location and, means coupled tosaid sample tubing means and responsive to said signal levels for movingthe output end of said sample tubing to said test site when saiddetected signal is indicative of the presence of sample as contained insaid third volume whereby only sample is directed to said test site whensaid output end of said sample tubing is moved and for dispensing saidwashing fluid, immiscible medium in response to said signal levels whensample is not detected.
 16. The apparatus according to claim 15, whereinsaid immiscible medium is air and said body fluid is blood.
 17. Theapparatus according to claim 15, wherein said washing fluid isinjectable normal saline.
 18. The apparatus according to claim 15,wherein said first sample input port is coupled to a catheter forinsertion into the blood vessel of a patient.
 19. The apparatusaccording to claim 15, wherein said first sample input port is coupledto a source of extracorporeal blood flow.
 20. The apparatus according toclaim 15, wherein said second washing fluid input port is coupled to oneend of a flexible tube with the other end coupled to a washing fluidreservoir.
 21. The apparatus according to claim 15, wherein said sampletubing means includes second pumping means for moving said sequence ofmaterial from said sample output port.
 22. The apparatus according toclaim 21, wherein said second pumping means is a peristaltic pump. 23.The apparatus according to claim 15, wherein said sample tubing meanshas a nozzle located at said output end for dispensing said materials.24. The apparatus according to claim 15, wherein said tubing meansincludes a cassette housing for holding a sample tubing means and awashing fluid tube section between input and output ports of saidcassette housing and having an aperture across which said sample andwashing fluid tube sections are directed to enable said tubes to contactsaid pumping means when said cassette is placed in a predeterminedposition with respect to said pumping means.
 25. The apparatus accordingto claim 15, further including detecting means positioned near saidfirst input port and operative to detect bubbles in said fluid manifoldmeans to provide a signal output indicative of a problem condition andmeans coupled to said control means and responsive to said signal toprevent said energization of said first and second pump means.
 26. Theapparatus according to claim 15 wherein said fluid manifold meansincludes valve means coupled to said washing fluid and sample tubes toassure unidirectional flow and including said first pump means fordirecting a predetermined volume of air into said sample tube.
 27. Amethod of transporting a sample of body fluid from a first location to aremote location including a test site, comprising the stepof:positioning a flexible tube between said first location and saidremote location indicative of a body fluid sample carrying line, joiningsaid tube at said first location to a source of body fluid at one point,a source of immiscible fluid at another point and a source of washingfluid at still another point, first directing washing fluid through saidtube to cause said washing fluid to travel through said tube to entersaid first location and simultaneously directing washing fluid towardssaid remote location, then removing body fluid from said first locationand directing said fluid towards said remote location, then directing afirst volume of immiscible fluid into said tube to provide a barrierbetween said sample and said washing fluid and then directing a secondvolume of immiscible fluid into said tube to provide another barrier bylocating said sample between said barriers and then directing anothervolume of washing fluid into said tube, detecting said sample as locatedbetween said barriers at said remote location and depositing said sampleas detected at said test site, then directing washing fluid through saidtube to cause the washing fluid to travel simultaneously toward saidfirst location and said remote location from said source of washingfluid and introducing a series of said immiscible bubbles in the fluidas directed toward said remote location to wash said sample tube of bodyfluid deposits prior to repeating the step of first directing.
 28. Themethod according to claim 27, wherein the step of directing immisciblefluid includes pumping a predetermined volume of fluid into said tube toprovide a given volume barrier.
 29. The method according to claim 27,wherein the steps of directing includes pumping said fluids through saidtube as directed into said tube.
 30. The method according to claim 28,wherein pumping is accommodated by peristaltic pumping.
 31. The methodaccording to claim 28, further wherein the step of detecting includesdetecting all fluids in said tube at said remote location to determinefluids which are not sample fluid, anddischarging said fluids from saidtube at said remote location or waste fluids.
 32. The method accordingto claim 31, wherein said waste fluids are discharged at a waste site.33. The method according to claim 31, wherein sample fluid is dischargedat a test site.
 34. The method according to claim 31, wherein samplefluid is discharged at a sample site.